Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results.

PURPOSE: EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer. PATIENTS AND METHODS: This randomized phase II, two-part, multicenter trial included newly diagnosed women with HER2-positive invasive breast cancer due to undergo surgery. Patients were randomized to: part 1 (1:2:2), no treatment (control), trastuzumab or lapatinib; part 2 (1:1:2) control, trastuzumab, or lapatinib and trastuzumab combination. Treatment was given for 11 days presurgery. Coprimary endpoints were change in Ki67 and apoptosis between baseline and surgery tumor samples (biologic response: ≥30% change). Central pathology review scored residual cancer burden (RCB). Relapse-free survival (RFS) explored long-term effects. RESULTS: Between November 2010 and September 2015, 257 patients were randomized (part 1: control 22, trastuzumab 57, lapatinib 51; part 2: control 29, trastuzumab 32, combination 66). Ki67 response was evaluable for 223 patients: in part 1 Ki67 response occurred in 29/44 (66%) lapatinib versus 18/49 (37%) trastuzumab (P = 0.007) and 1/22 (5%) control (P < 0.0001); in part 2 in 36/49 (74%) combination versus 14/31 (45%) trastuzumab (P = 0.02) and 2/28 (7%) control (P < 0.0001). No significant increase in apoptosis after 11 days was seen in treatment groups. Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group. After 6 years median follow-up, 28 (11%) had recurrence and 19 (7%) died. No recurrences or deaths were observed among patients who achieved a pCR. Ki67% falls ≥50% associated with fewer recurrences (P = 0.002). CONCLUSIONS: Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation.

Will adherence to new guidance lead to missed cancer diagnoses? Evaluation of limiting symptomatic mammograms to over forties.

Within the United Kingdom, a recent change in "Best Practice Guidance" has suggested that mammograms for symptomatic breast patients, with a clinically benign examination, should be limited to those over 40 years . This has led to anxiety over missing cancer diagnoses in the 35-39 year-old age group. This study aimed to assess the impact of the new guidance upon a NHS Breast unit with a particular focus on safety. Two cancer data bases (BASO and SOMERSET) were used to identify thirty-three patients aged 35-39 years diagnosed with breast cancer between January 2007 and June 2011. Case notes were retrieved and retrospectively analyzed for trends during clinical (P1-P5) and radiological assessment (using Royal College Radiologists Breast Group classification-M1-5, U1-5). Sensitivity and false-negative rates for each modality were calculated. Sensitivities of clinical examination, mammography, and ultrasound for detecting malignancy were 72.7%, 78.8%, and 93.9%, respectively. Within the clinically benign group (P1 and P2), mammography and ultrasound showed sensitivities of detecting malignancy of 55.5% and 88.9%, respectively, with three extra cancers being identified by ultrasound when mammography was graded less than M3 (indeterminate lesion-requiring biopsy). Importantly, no cancers would have been missed if the new guidance had been adhered to. This study has shown that mammography has no additional diagnostic benefit as first-line imaging in symptomatic breast patients aged 35-39 years. It has confirmed that implementation of the new Best Practice Guidance is safe, when used in the setting of triple assessment, to ensure cancer diagnoses are not missed.